Lymphocytes become infected with Epstein-Barr virus during the course of primary human infection. Following primary infection the virus remains latent within lymphocytes. Lymphocytes which have been infected with EBV in vitro can be grown in vitro as continuous lymphoblastoid cell lines. Progeny cells contain EBV DNA, an intranuclear antigen, and the capacity for continued growth in culture, but there is usually little evidence of virus replication. A similar state of virus infection in lymphocytes in which there is expression of an intranuclear antigen without evidence of virus replication pertains in Burkitt tumor tissue. Continued growth of cells infected with EBV requires tight regulation of expression of those virus genes which are expressed during virus replication and which cause cell death. The long-range goal of this research program is to elucidate the biochemical mechanisms involved in the regulation of expression of EBV DNA.